Methylation is an important determinant of metal toxicity, the striking example being the far greater hazards of MeHg+ and Me2Hg versus Hg2+. Other energy and industrially related metals can also be methvlated, either in the environment or within mammalian tissues. It may be a means for the metabolic detoxification of As. We have studied the biochemical methylation of Pt, Cr, and Ti and will begin to investigate the mechanism by which As is methylated in mammalian cells. Toxicity studies are focusing on metal compound effects at the cellular and genetic levels. For their many advantegeous properties Chinese hamster ovary (CHO) lines are being employed as the in vitro cell system. Our primary goal is to assess quantitatively the influence of methylation and valence state on the mutagenicities of select metals that are likely to be released in larger amounts from the accelerated utilizationof coal, further pesticide management with arsenicals, and increased industrial waste-water pollution in general. The list of metals, three of which are already known to be carcinogenic, includes As, /Cr, Hg, Mn, Pb, Sn, Tl, and perhaps Se. Mutagenicity is being assayed at two independent genetic sites, the CHO/HGPRT locus and a CHO auxotrophic reversion locus. The latter is being developed and validated under this project as a supplemental system for testing metal mutagenicity. A second major objective is to determine the biological methyl group donor in mammalian As methylation and the possible interrelationship between As cellular toxicity and folate-dependent/l-carbon metabolism.